title: The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments.
abstract: BACKGROUND
  No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes--the "sentinel lesion approach".
  
  
  METHODS
  MSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway.
  
  
  RESULTS
  Ten participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm.
  
  
  CONCLUSIONS
  In addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS--the sentinel lesion approach--serving as proof of principle for its future wider applicability.
  
  
  BACKGROUND
  ClinicalTrials.gov (NCT00395200).
authors.affiliation: Dept, of Clinical Neurosciences, University of Cambridge, UK. pc349@cam.ac.uk
authors.forename: Peter
authors.initials: P
authors.lastname: Connick
authors.forename: Madhan
authors.initials: M
authors.lastname: Kolappan
authors.forename: Rickie
authors.initials: R
authors.lastname: Patani
authors.forename: Michael A
authors.initials: MA
authors.lastname: Scott
authors.forename: Charles
authors.initials: C
authors.lastname: Crawley
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: He
authors.forename: Karen
authors.initials: K
authors.lastname: Richardson
authors.forename: Kelly
authors.initials: K
authors.lastname: Barber
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Webber
authors.forename: Claudia A M
authors.initials: CA
authors.lastname: Wheeler-Kingshott
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Tozer
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Samson
authors.forename: David L
authors.initials: DL
authors.lastname: Thomas
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Du
authors.forename: Shi L
authors.initials: SL
authors.lastname: Luan
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Michell
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Altmann
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
authors.forename: Alastair
authors.initials: A
authors.lastname: Compston
authors.forename: Siddharthan
authors.initials: S
authors.lastname: Chandran
mesh_terms: D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D004185:Disability Evaluation; D004739:England; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000601:surgery*; D012107:Research Design; D018570:Risk Assessment; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome